An international research team has made a major discovery that a rare inherited bleeding syndrome is caused by a gene mutation – but researchers were also surprised to find a link between the mutation and certain types of cancer.
The syndrome results in a low number of platelets in the blood, or cells that help blood to clot, and the only treatment is lifelong blood transfusions.
The study was published today in Science Translational Medicine and the research team includes Professor Wendy Erber, Dean of UWA’s Faculty of Medicine, Dentistry and Health Sciences.
Professor Erber said firstly identifying the genes was important because it would mean that patients could be diagnosed accurately and early, reducing the rate of disease progression.
“In addition, the significance of finding a cause means that there is the potential for improved treatment to specifically target the genetic abnormality,” she said.
“Given it was found that the mutated gene causes a certain type of protein to be hyperactive, inhibiting the activity of this protein could potentially eliminate the need for blood transfusions, which is the only treatment currently available.”
Professor Erber said researchers studied three generations of the same family where certain members suffered from excessive unexplained bleeding, as well as abnormal bones and disruption to tooth development.
Professor Erber said such patients had long presented a mystery to the medical profession and their illness had often been misdiagnosed because nobody had found what caused the bleeding.
“Even with the best pathology testing available, no explanation or cause had ever been identified for what appeared to be an inherited condition,” she said.
“Very thorough DNA testing was done to find the rogue gene. It was found that all the patients had the same mutation in a gene, called SRC, and this led to the gene being hyperactive.”
Professor Erber said the mutation explained why the family members were experiencing the same problem and would enable researchers to test others for the same condition.
“This is of value in itself but there was also a surprise finding – that mutations identified in this inherited syndrome are also associated with certain types of cancers. However, when the DNA mutation occurs in cancer it is acquired, not inherited,” she said.
“The importance of this surprise finding is that research on the cancers with the same gene mutation is rather advanced and this knowledge may be transferred to the patients with the bleeding syndrome. Cancer research has already developed an inhibitor for the protein that becomes overactive.”
Professor Erber’s major role in the study was reviewing the blood counts and reviewing patient samples of blood and bone marrow. The samples were sent from Europe to UWA because of her expertise in this area of haematology.
The next step for researchers was to explore whether there was a link between this mutation and the bleeding risk common in patients taking cancer drugs that might interfere with the SRC mutation, she said.
“The vision is to then use the latest cancer research findings related to drugs that inhibit the hyperactive protein associated with gene mutations and potentially eliminate the requirement for regular blood transfusions in patients with the bleeding syndrome,” Professor Erber said.
The research was undertaken by the international BRIDGE-BPD consortium, which aims to discover gene mutations associated with inherited rare blood diseases with no known cause. Project leaders were Professor Willem Ouwehand, from Cambridge University and Professor Kathleen Freson, from Leuven University in Belgium.
Professor Wendy Erber (+61 8) 9346 3928 / (+61 4) 18 610 600
(Dean of Faculty of Medicine, Dentistry and Health Sciences)
David Stacey (UWA Media and Public Relations Manager) (+61 8) 6488 3229 / (+61 4) 32 637 716